Combined Rituximab and Lenalidomide Treatment for Untreated Patients With Follicular Lymphoma

NCT01476787 | Completed Phase 3 Results DMC

• 2 other identifiers: RV-FOL-GELARC-0683C2011-002792-42
• Study Type: interventional
• Target: 1,030
• Locations: 2 countries
• Sites: 36

Brief Summary

The purpose of this study is to evaluate the effect of the combined treatment of lenalidomide and rituximab in controlling the Follicular Lymphoma disease and also increase the length of response compared to the available standard combination chemotherapy treatment for Follicular Lymphoma.

Conditions

Follicular Lymphoma

Keywords

Follicular lymphoma; Non-Hodgkins Follicular Lymphoma; treatment for Follicular Lymphoma; rituximab treatment; rituximab and lenalidomide treatment

Outcome Measures

Primary Outcomes (2)

• Complete Response Rate (CR/CRu) at 120 Weeks by Independent Central Review

  The Complete Response Rate (CR/CRu) is the percentage of participants who achieve complete response (CR/CRu) at 120 weeks as assessed per Independent Central Review. * Complete Response (CR): Disappearance of all evidence of disease. * Complete Response Unconfirmed (CRu): Disappearance of all disease with the exception of residual lymph nodes that are 1.5 cm or less in greatest transverse diameter and/or indeterminate bone marrow findings.

  At 120 weeks

• Progression-free Survival (PFS)

  Progression-free survival (PFS) is defined as the time from randomization into the study to the first observation of documented disease progression or death due to any cause. Progressive Disease (PD) is characterized by any of the following: * An increase of at least 50% in the sum of the products of the greatest diameters (SPD) of any previously identified abnormal lymph node(s) or other disease sites. * The appearance of any new lesion during or after treatment. * An increase of at least 50% in the longest diameter of a previously identified node that was 1 cm or more in its short axis. * An increase of at least 50% in the size of other lesions (e.g., splenomegaly, hepatomegaly). Based on Kaplan-Meier estimates.

  From randomization into the study to the first observation of documented disease progression or death due to any cause (up to approximately 140 months).

Secondary Outcomes (4)

• Complete Response Rate (CR) at 120 Weeks Per Independent Central Review

  At 120 weeks

• Event-free Survival (EFS)

  From randomization to the date of first documented progression, relapse, and initiation of a new anti-lymphoma treatment or death by any cause (up to approximately 140 months).

• Overall Survival (OS)

  From randomization to the date of death by any cause (up to approximately 144 months).

• Time to Next Anti-Lymphoma Treatment (TTNLT)

  From the date of randomization to the date of the first documented administration of any new anti-lymphoma treatment (up to approximately 140 months).

Study Arms (2)

Lenalidomide + Rituximab

EXPERIMENTAL

* Lenalidomide dose 20-mg on days 2-22 every 28 days for 6 cycles, if CR then 10-mg on days 2-22 every 28 days for 12 cycles. PR after 6 cycles, continue 20 mg for 3\~6 cycles and then 10 mg on days 2-22 every 28-day cycles for up to 18 cycles. * Rituximab, 375 mg/m2 on days 1, 8, 15 and 22 of cycle 1, day 1 of cycles 2 to 6; 8 weeks later responding patients continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles.

Drug: Rituximab; Drug: Lenalidomide

Control

ACTIVE COMPARATOR

• ONE of the following: Rituximab-CHOP, Rituximab-CVP, Rituximab-Bendamustine. 7 to 8 weeks later responding patients will continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles.

Drug: Rituximab-CHOP; Drug: Rituximab-CVP; Drug: Rituximab-Bendamustine

Interventions

Rituximab DRUG

375 mg/m2 on days 1, 8, 15 and 22 of cycle 1, day 1 of cycles 2 to 6; 8 weeks later responding patients continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles.

Lenalidomide + Rituximab

Lenalidomide DRUG

20-mg on days 2-22 every 28 days x 6 cycles, if CR then 10-mg on days 2-22 every 28 days for 12 cycles. PR after 6 cycles, continue 20 mg for 3\~6 cycles and then 10 mg on days 2-22 every 28-day cycles for upto 18 cycles

Also known as: Revlimid

Lenalidomide + Rituximab

Rituximab-CHOP DRUG

7 to 8 weeks later responding patients will continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles.

Control

Rituximab-CVP DRUG

7 to 8 weeks later responding patients will continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles.

Control

Rituximab-Bendamustine DRUG

7 to 8 weeks later responding patients will continue with 375 mg/m2 rituximab every 8 weeks for 12 cycles.

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed follicular lymphoma grade 1, 2 or 3a, Stage II-IV
• Have no prior systemic treatment for lymphoma
• Symptomatic follicular lymphoma requiring treatment.
• Age ≥18 years
• Eastern Cooperative oncology group performance status 0-2
• Willing to follow pregnancy precautions

You may not qualify if:

• Clinical evidence of transformed lymphoma or Grade 3b follicular lymphoma.
• Major surgery (excluding lymph node biopsy) within 28 days prior to signing informed consent.
• Known seropositive for or active viral infection with hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV)
• Known sensitivity or allergy to murine products.
• Presence or history of central nervous system involvement by lymphoma
• At high risk for a venous thromboembolic event (VTE) and not willing to take VTE prophylaxis
• Any of the following laboratory abnormalities:
• serum aspartate transaminase or alanine transaminase \> 3x upper limit of normal (ULN), except in patients with documented liver involvement by lymphoma
• total bilirubin \> 2.0 mg/dl (34 µmol/L) except in cases of Gilberts Syndrome and documented liver or pancreatic involvement by lymphoma
• creatinine clearance of \< 30 mL/min

Sponsors & Collaborators

• Celgene: lead
• The Lymphoma Academic Research Organisation: collaborator

Study Sites (36)

Local Institution - 54103

Chandler, Arizona, 85224, United States

Location

Local Institution - 51803

Fullerton, California, 92835, United States

Location

Local Institution - 52003

Los Angeles, California, 90095, United States

Location

Local Institution - 51603

Colorado Springs, Colorado, 80909, United States

Location

Local Institution - 52503

Englewood, Florida, 34223, United States

Location

Local Institution - 51703

Orlando, Florida, 32806, United States

Location

Local Institution - 53803

St. Petersburg, Florida, 33705, United States

Location

Local Institution - 50803

Chicago, Illinois, 60657, United States

Location

Local Institution - 52203

Lexington, Kentucky, 40536, United States

Location

Local Institution - 53603

Westminster, Maryland, 21157, United States

Location

Local Institution - 50403

Boston, Massachusetts, 02114, United States

Location

Local Institution - 50503

Boston, Massachusetts, 02114, United States

Location

Local Institution - 53003

Southfield, Michigan, 48075, United States

Location

Local Institution - 51003

St Louis, Missouri, 63110, United States

Location

Local Institution - 54403

Cherry Hill, New Jersey, 08003, United States

Location

Local Institution - 53703

Hackensack, New Jersey, 07601, United States

Location

Local Institution - 50903

Morristown, New Jersey, 07960, United States

Location

Local Institution - 54303

Sparta, New Jersey, 07871, United States

Location

Local Institution - 52403

New York, New York, 10019, United States

Location

Local Institution - 50203

New York, New York, 10021, United States

Location

Local Institution - 51303

Nashville, Tennessee, 37203, United States

Location

Local Institution - 51203

Dallas, Texas, 75246, United States

Location

Local Institution - 51103

Houston, Texas, 77030, United States

Location

Local Institution - 54003

Lubbock, Texas, 79410, United States

Location

Local Institution - 53303

Richmond, Virginia, 23230, United States

Location

Local Institution - 52703

Seattle, Washington, 98109, United States

Location

Local Institution - 40722

Chuo-ku, Tokyo, 104-0045, Japan

Location

Local Institution - 40222

Koto-ku, Tokyo, 1358550, Japan

Location

Local Institution - 41122

Minato-ku, Tokyo, 105-8470, Japan

Location

Local Institution - 40922

Fukuoka, 812-8582, Japan

Location

Local Institution - 40422

Hiroshima, 7200001, Japan

Location

Local Institution - 40122

Isehara City, Kanagawa, 259-1193, Japan

Location

Local Institution - 40322

Kobe, 650-0047, Japan

Location

Local Institution - 40622

Kyoto, 602-8566, Japan

Location

Local Institution - 41022

Sendai, 983-8520, Japan

Location

Local Institution - 40522

Shizuoka, 410-2295, Japan

Location

Related Publications (5)

• Morschhauser F, Fowler NH, Feugier P, Bouabdallah R, Tilly H, Palomba ML, Fruchart C, Libby EN, Casasnovas RO, Flinn IW, Haioun C, Maisonneuve H, Ysebaert L, Bartlett NL, Bouabdallah K, Brice P, Ribrag V, Daguindau N, Le Gouill S, Pica GM, Martin Garcia-Sancho A, Lopez-Guillermo A, Larouche JF, Ando K, Gomes da Silva M, Andre M, Zachee P, Sehn LH, Tobinai K, Cartron G, Liu D, Wang J, Xerri L, Salles GA; RELEVANCE Trial Investigators. Rituximab plus Lenalidomide in Advanced Untreated Follicular Lymphoma. N Engl J Med. 2018 Sep 6;379(10):934-947. doi: 10.1056/NEJMoa1805104.

  PMID: 30184451 BACKGROUND

• Fowler NH, Davis RE, Rawal S, Nastoupil L, Hagemeister FB, McLaughlin P, Kwak LW, Romaguera JE, Fanale MA, Fayad LE, Westin JR, Shah J, Orlowski RZ, Wang M, Turturro F, Oki Y, Claret LC, Feng L, Baladandayuthapani V, Muzzafar T, Tsai KY, Samaniego F, Neelapu SS. Safety and activity of lenalidomide and rituximab in untreated indolent lymphoma: an open-label, phase 2 trial. Lancet Oncol. 2014 Nov;15(12):1311-8. doi: 10.1016/S1470-2045(14)70455-3. Epub 2014 Oct 15.

  PMID: 25439689 BACKGROUND

• Ahmadi T, Chong EA, Gordon A, Aqui NA, Nasta SD, Svoboda J, Mato AR, Schuster SJ. Combined lenalidomide, low-dose dexamethasone, and rituximab achieves durable responses in rituximab-resistant indolent and mantle cell lymphomas. Cancer. 2014 Jan 15;120(2):222-8. doi: 10.1002/cncr.28405. Epub 2013 Oct 7.

  PMID: 24122387 BACKGROUND

• Delfau-Larue MH, Boulland ML, Beldi-Ferchiou A, Feugier P, Maisonneuve H, Casasnovas RO, Lemonnier F, Pica GM, Houot R, Ysebaert L, Tilly H, Eisenmann JC, Le Gouill S, Ribrag V, Godmer P, Glaisner S, Cartron G, Xerri L, Salles GA, Fest T, Morschhauser F. Lenalidomide/rituximab induces high molecular response in untreated follicular lymphoma: LYSA ancillary RELEVANCE study. Blood Adv. 2020 Aug 11;4(14):3217-3223. doi: 10.1182/bloodadvances.2020001955.

  PMID: 32673385 BACKGROUND

• Laurent C, Trisal P, Tesson B, Seth S, Beyou A, Roulland S, Lesne B, Van Acker N, Cerapio JP, Chartier L, Guille A, Stokes ME, Huang CC, Huet S, Gandhi AK, Morschhauser F, Xerri L. Follicular lymphoma comprises germinal center-like and memory-like molecular subtypes with prognostic significance. Blood. 2024 Dec 12;144(24):2503-2516. doi: 10.1182/blood.2024024496.

  PMID: 39374535 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

Rituximab; Lenalidomide

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please Email

Study Officials

• Franck Morschhauser, MD, PhD

  The Lymphoma Study Association (LYSA)

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2011
• First Posted: November 22, 2011
• Study Start: December 29, 2011
• Primary Completion: April 30, 2024
• Study Completion: April 30, 2024
• Last Updated: May 14, 2025
• Results First Posted: May 14, 2025

Record last verified: 2025-04

Locations

JP (10); US (26)